Individual data from 31 trials and 11,644 women. In high-risk single pregnancies, vaginal progesterone lowered birth before 34 weeks (risk ratio 0.78) and 17-OHPC showed a smaller, borderline effect (0.83). Oral progesterone had too little evidence, and progestogens were not supported for unselected twins or triplets.
the research library food, supplements and pregnancy
pregnancy, first trimester and beyond
You deserve the actual trials, not the forum version.
Pregnancy is where confident wellness advice can do the most damage, because it can crowd out real obstetric care. This page is a reading list of the trials themselves, so you and your clinician can look at the same numbers.
please read this first
This page is research, not medical advice. Progesterone is a prescription decision that belongs to you and your OB or midwife, and nothing here should change what you take without that conversation. If you are bleeding or in pain, call your care team.
12papers
11studies in people
5counterpoints
this page, by tier
- 10 human evidence
- 1 early human
- 0 lab + animal
- 1 background
the short version
what the research found
the headline numbers
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In 836 women with unexplained recurrent miscarriage, first-trimester vaginal progesterone gave live births in 65.8% versus 63.3% on placebo, not a significant difference.
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In 4,153 women bleeding in early pregnancy, live birth was 75% with progesterone versus 72% with placebo, just short of significance.
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In women with three or more previous miscarriages and current bleeding, live birth was 72% with progesterone versus 57% with placebo.
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Across 31 trials and 11,644 women, vaginal progesterone lowered birth before 34 weeks in high-risk single pregnancies by about 22%.
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The confirmatory 17-OHPC trial found preterm birth before 35 weeks in 11.0% versus 11.5% on placebo, and the drug's approval was later withdrawn.
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In women who had a previous pregnancy affected by a neural tube defect, folic acid around conception cut the chance of it happening again by 72%.
my honest bottom line
Progesterone did not raise live birth rates overall in either large first-trimester trial; the signal sits in women with three or more previous miscarriages who are bleeding now. Folic acid around conception has the strongest prenatal nutrient result on this page. The biggest limitation is that subgroup findings raise questions rather than settle them, and the decision belongs to you and your obstetric team, not a website.
evidence at a glance
12 papers
- human evidence10
- early human1
- lab + animalnone yet0
- background1
Includes 5 counterpoints.
every title links to the original
the papers
Sorted from the strongest human evidence down to the lab work and background reading. Counterpoints are marked, and they stay in on purpose.
A pooled look at PROMISE and PRISM. In women with any previous miscarriage and current bleeding, live birth was 75% with progesterone versus 70%. With three or more previous miscarriages and bleeding it was 72% versus 57%. The authors found no short-term safety concerns.
The confirmatory trial for 17-OHPC, in 1,708 women with a previous preterm birth. Birth before 35 weeks was 11.0% versus 11.5% on placebo, with no differences in newborn complications or deaths. It did not confirm the 2003 result.
4,153 women with bleeding in early pregnancy used vaginal progesterone 400 mg twice daily or placebo. Live birth after at least 34 weeks was 75% versus 72%, which missed statistical significance (P = 0.08). Side effects did not differ.
A Cochrane review of 70 trials and 19,927 women. Omega-3 in pregnancy lowered births before 37 weeks by 11% and before 34 weeks by 42%, graded high-quality evidence, and slightly raised pregnancies running past 42 weeks (2.6% versus 1.6%).
1,300 pregnancies in Bangladesh were randomized to weekly vitamin D at one of three doses or placebo, some continuing after birth. Infant length at one year did not differ, vitamin D levels rose as expected, and the highest dose group had more possible excess calcium in the urine.
show all 12 papersshow fewer
832 mildly iodine-deficient pregnant women in India and Thailand took 200 µg of iodine daily or placebo from about 11 weeks. At age 5 to 6, their children's IQ and executive function did not differ.
836 women with unexplained recurrent miscarriage used vaginal progesterone or placebo in the first trimester. Live births were 65.8% versus 63.3%, a difference of 2.5 points that was not significant. Side effects did not differ.
Women with a previous spontaneous preterm birth got weekly 17-OHPC injections or placebo. Birth before 37 weeks was 36.3% versus 54.9%, and babies had fewer serious newborn complications. This single trial became the basis for the drug's accelerated approval.
1,817 women who had already had a pregnancy affected by a neural tube defect took folic acid, other vitamins, both or neither around conception. There were 6 affected pregnancies in the folic acid groups versus 21 in the others, a 72% lower risk. The other vitamins showed no significant effect.
26 women ate a controlled diet with 930 mg or 480 mg of choline a day in the third trimester. Babies of the higher-choline mothers had faster reaction times across four test ages in the first year. It is very small, and it measured processing speed, not later outcomes.
An editorial walking through how 17-OHPC won accelerated approval in 2011 on a single trial, why a confirmatory trial was required, the 9 to 7 advisory committee vote in October 2019 to withdraw approval after PROLONG, and the withdrawal that followed.
keep reading
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This page summarizes published research for education. It is not medical advice. Please make any decision about progesterone, supplements or prenatal care with your OB or midwife. Summaries by Dr. Kaylan Jackson, PhD, a chemist, not a physician. Citations checked against PubMed and Crossref, September 2026.